Skin, Autoimmunity and Inflammation: A Comprehensive Exploration through Scientific Research.

Human skin, as the body's largest organ, orchestrates a multifaceted interplay of cellular interactions that regulate essential physiological processes, including inflammation, immune responses, wound healing, and angiogenesis [...].

The ATTRACT study: screening for the early identification of axial psoriatic arthritis in a cohort of Italian psoriatic patients.

OBJECTIVE: There is growing interest in the early identification of patients with axial psoriatic arthritis (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. METHODS: The dermatologist-centered screening (DCS) questionnaire was administrated by Dermatologists to consecutive patients fulfilling the inclusion criteria (1. age ≥ 18 years and 2. clinical diagnosis of psoriasis made by a dermatologist) to identify patients eligible (affirmative answers 1-3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic, and imaging data were collected from all referred patients. RESULTS: Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months, and 140 (53%) reporting back pain onset before the age of 45. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients.Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with Pso without PsA. CONCLUSION: The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA.

InflammamiR-146a and -155 Plasma Levels are Associated with Clinical Efficacy of Risankizumab Treatment in Psoriatic Patients: Pilot Study.

INTRODUCTION: The key role of microRNAs (miRNAs) in the pathogenesis of psoriasis has been extensively discussed in the literature. Increasing evidence suggests that the analysis of miRNA levels may constitute an innovative approach for exploring the clinical efficacy of anti-inflammatory therapies in patients with psoriasis. However, so far there have been no published studies evaluating the effects of modulating circulating miRNAs and the efficacy of anti-interleukin-23 (anti-IL-23) therapy. The main objective of the present was to evaluate the diagnostic/prognostic relevance of the levels of five circulating candidate miRNAs (miR-21, miR-146a, miR-155, miR-210, miR-378) in psoriatic patients treated with the anti-IL-23 drug risankizumab. METHODS: A total of eight psoriatic participants were recruited consecutively from January 2021 to July 2021 at the Dermatology Clinic of Università Politecnica delle Marche (UNIVPM) "Ospedali Riuniti" of Marche. Data on anamnestic, clinical and miRNA evaluations before the initiation of risankizumab therapy and after 1 year (January 2021-July 2022) of risankizumab therapy were available for all patients. RESULTS: A significant reduction in the signs and symptoms in patients treated with risankizumab was observed after 1 year of treatment, suggesting that the drug is effective for treating psoriasis in a context of real-life clinical evaluation. Plasma levels of the two prototypical inflammamiRs, miR-146a and miR-155, were significantly reduced after 1 year of risankizumab therapy. Also, in patients before treatment, a significant positive correlation was found between circulating levels of miR-210 and miR-378 and disease severity scores. CONCLUSIONS: Our results reinforce the notion that specific circulating miRNAs could have clinical relevance as diagnostic/prognostic biomarkers of psoriatic disease and suggest the potential relevance of these miRNAs as biomarkers of treatment response.

miRNAs, Mesenchymal Stromal Cells and Major Neoplastic and Inflammatory Skin Diseases: A Page Being Written: A Systematic Review.

Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.

New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. It is accompanied by pain, malodourous secretion and a dramatically decreased quality of life. Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. Since the registration of the tumor necrosis factor-alpha inhibitor Adalimumab in 2015, several cytokines have been implicated in the pathomechanism of HS and the research of novel therapeutic targets has been intensified. We provide an update on the inflammatory cytokines with a central role in HS pathogenesis and the most promising target molecules of future HS management.

Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art.

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

Efficacy and Safety of Botulinum Toxin B in Focal Hyperhidrosis: A Narrative Review.

Botulinum toxin type B (BoNT-B), known as Myobloc® in the United States and as Neurobloc® in Europe, is a new therapeutically available serotype among the botulinum toxin family. During the last years several data have been reported in literature investigating its efficacy and safety, as well as defining the dosing and application regiments of BoNT-B in the treatment of hyperhidrosis. Moreover, recent studies have been examining its safety profile, which may be different from those known about BoNT-A. The aim of this review is to provide information about what is currently known about BoNT-B in regards to the treatment of focal hyperhidrosis.

Mesenchymal Stem Cells and Psoriasis: Systematic Review.

Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton's jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease.

A Systematic Review of Atopic Dermatitis: The Intriguing Journey Starting from Physiopathology to Treatment, from Laboratory Bench to Bedside.

Atopic dermatitis (AD) is a common chronic inflammatory and immune-mediated skin disease with a complex pathophysiology and still represents a therapeutic challenge, owing to limited responses to available treatments. However, recent advances in the understanding of AD pathophysiology have led to the discovery of several new potential therapeutic targets, and research in the field of new molecules with therapeutic perspectives is boiling, with more than 70 new promising drugs in development. The aim of this systematic review is to provide the state of the art on the current knowledge concerning the pathophysiology of the disease and on novel agents currently being investigated for AD, and to highlight which type of evolution is going to take place in therapeutic approaches of atopic dermatitis in the coming years.

Atypical Scleroderma-like Chronic GVHD in a Liver Transplant Patient, Clinical and MRI Correlations.

Dear Editor, cutaneous chronic graft versus host disease (cGVHD) is a pathological process consisting of donor-derived T-cells aimed at the antigens of the recipient. It exhibits a large range of clinical presentations resembling morphea and deep sclerosis/fasciitis, all characterized by both inflammation and progressive dermal and hypodermic fibrosis (1). Although classic scleroderma-like lesions in cGVHD are nummular or irregular plaques and linear bundles associated with hypo- or hyperpigmentation (2), we report an atypical case with ulcerative presentation. No other case-reports of morphea-like or scleroderma-like cGVHD with an ulcerated appearance after liver transplantation (LT) and magnetic resonance imaging (MRI) correlation have been found in the literature. CASE REPORT Ten months after LT due to an end-stage cirrhosis associated with multifocal hepatocarcinoma (HCC), a 61-year-old man on immunosuppressive therapy with Tacrolimus (1 mg) and Everolimus (10 mg) presented to our clinic for a skin lesion in the right scapular region. We observed a flat ulcerated plaque with areas of sclerosis, minimal necrosis, and well-defined slightly erythematous margins (Figure 1, a). On palpation, the plaque had a hard consistency and was slightly painful. The skin lesion had been preceded by subjective discomfort with stinging sensation for seven months before its onset. Gradually lesion developed starting from a small, flat, oval purplish plaque associated with a progressive increase in pain. Patient denied dysphagia, retrosternal heartburn, Raynaud's phenomenon, arthralgia, and dyspnea. A previous MRI (Figure 2, a,b) showed subcutaneous and muscle edema. Blood tests showed abnormal liver function indexes due to extrahepatic cholestasis, while C-reactive protein, erythrocyte sedimentation rate, and leukocytes were within normal ranges. Self-reactive antibodies were negative. Histological examination (Figure 1, b) identified rare dyskeratotic keratinocytes and basal lymphocyte infiltrate, a dermal dense fibrosis with the disappearance of the skin appendages, and large fibrous septa in the adipose panniculus. It led to the diagnosis of scleroderma/morphea, based on the patient's clinical history. The diagnosis of graft versus host disease scleroderma-like post liver transplant was established. The lesion was treated by topical application of 0.05% clobetasol once a day. We did not use systemic immunosuppressive therapy in order to prevent HCC recurrence. The patient is currently in clinical follow-up to identify worsening or neoplastic degeneration. CASE DISCUSSION Cutaneous cGVHD often presents clinically as an ulcerative evolution in the context of fibrosis and diffuse skin atrophy (2), but very rarely initially appears as a well-delimited ulcerated plaque. Only few cases of ulcer have been found in literature, all in patients undergoing hematopoietic stem cell transplantation (HSCT), which is associated with the highest risk of developing GVHD, 20-50% (3,4), while LT has quite low incidence, at 0.5-2% (5). To our knowledge, this is the first case report of a scleroderma-like cGVHD lesion with ulcer appearance in LT. Our patient underwent two MRIs during post-transplant follow-up, which allowed us to evaluate the deep disease evolution. The T2-weighted MRI (Figure 2, c,d) performed approximately 1 year after transplantation, demonstrated fibrous septa in the subcutaneous fat and fascial thickening, with associated muscle hypotrophy and edema. The previous MRI, performed seven months after transplantation, already showed subcutaneous tissues and fascial edema, highlighting active inflammation. This evidence suggests that MRI could identify the lesion location before clinical manifestations, providing an opportunity to intervene promptly. To the best of our knowledge, this is the first reported case of cGVHD with atypical scleroderma-like presentation in a liver transplant patient whose clinical and MRI correlations have been traced. Our suggestions are supported by the results of other previous studies (6,7) evaluating MRI performance for assessing disease extent and activity, as well as therapeutic response in HSCT.

Biological Treatments for Pediatric Psoriasis: State of the Art and Future Perspectives.

Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and is associated with multiple comorbidities with a considerable reduction in quality of life of affected patients. One-third of psoriasis cases begin in childhood and are associated with significant medical comorbidities such as obesity, metabolic syndrome, arthritis, and psychiatric disorders. In addition, because of its chronic nature and frequent relapses, psoriasis tends to require long-term treatment. Treatment of pediatric psoriasis usually involves the same methods used for adults. However, most treatments for pediatric psoriasis are used off-label, and research in this regard is still lacking. Targeted therapies involving the use of newly developed biologic drugs are also increasingly being applied to childhood psoriasis. This review summarizes the clinical features of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and biological treatments of pediatric psoriasis.

Latest combination therapies in psoriasis: Narrative review of the literature.

Biological therapies revolutionized the treatment of many chronic inflammatory skin diseases, first of all psoriasis, thanks to their high efficacy and the reduced number of side effects. However, the use of a single biologic drug does not always provide complete control of the disease or associated comorbidities over time. The first biological drugs used for the treatment of psoriasis, tumor necrosis factor alpha inhibitors, have long been used in combination with traditional topical and systemic therapies to induce a complete remission of the disease that could not be achieved with innovative drug alone. Even with the advent of new biological therapies with more precise molecular targets, the challenge of using combination therapies remained. Psoriatic patients often have major comorbidities, such as arthritis, inflammatory bowel disease, uveitis or have other concomitant conditions such as chronic spontaneous urticaria and atopic dermatitis, which may require different biologic treatments than those indicated in psoriasis. The objective of this article is, through a comprehensive revision of the literature, to analyze in which cases the use of the combination of the latest therapies for psoriasis may be useful.

Mesenchymal Stem Cells Profile in Adult Atopic Dermatitis and Effect of IL4-IL13 Inflammatory Pathway Inhibition In Vivo: Prospective Case-Control Study.

Atopic dermatitis (AD) is an inflammatory disease that typically begins in childhood and may persist into adulthood, becoming a lifelong condition. The major inflammatory mediators of AD are known to be interleukin IL4 and IL13, so Dupilumab, which is able to inhibit both interleukins by blocking the shared IL4Rα subunit, has become an attractive option for treating AD. Mesenchymal stem cells (MSCs) are involved in the onset and development of AD by secreting specific interleukins. The aim of this study was to isolate MSCs from healthy controls (C-MSCs) and patients with AD before (AD-MSCs T0) and after 16 weeks of treatment with Dupilumab (AD-MSCs T16); to evaluate the expression mainly of IL4 and IL13 and of other inflammatory cytokines in C-MSCs, AD-MSCs at T0 and at T16; and to evaluate the efficacy of Dupilumab on MSCs immunobiology. C- and AD-MSCs (T0, T16) were isolated from skin specimens and characterized; the expression/secretion of IL4 and IL13 was evaluated using immuno-cytochemistry (ICC), indirect immune-fluorescence (IIF) and an ELISA test; secretion of IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, Interferon gamma (IFNγ), Tumor necrosis factor alpha (TNFα), Granulocyte Colony-Stimulating Factor (G-CSF), and Transforming Growth Factor beta1 (TGFß1) were measured with ELISA. IL13 and IL6 were over-expressed, while IL4 was down-regulated in AD-MSCs at T0 compared to C-MSCs. IL6 and IL13 expression was restored after 16 weeks of Dupilumab treatment, while no significant effects on IL4 expression were noted. Finally, IL2, IL5, IL10, IL12, IL17A, INFγ, TNFα, G-CSF, and TGFß1 were similarly secreted by C- and AD-MSCs. Although Dupilumab blocks the IL4Rα subunit shared by IL4 and IL13, it is evident that its real target is IL13, and its ability to target IL13 in MSCs reinforces the evidence, already known in differentiated cells, of the central role IL13 rather than IL4 in the development of AD. The inflammatory cascade in AD begins at the mesenchymal level, so an upstream therapeutic intervention, able to modify the immunobiology of atopic MSCs, could potentially change the natural history of the disease.

Should we be concerned about gastrointestinal-related adverse events in patients with plaque psoriasis receiving secukinumab therapy? A retrospective, real-life study.

Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data in psoriatic patients treated with secukinumab are lacking. A descriptive, retrospective study was performed by reviewing the medical records of patients who received secukinumab for plaque psoriasis for at least 1 year and who made a follow-up visit to the dermatology clinic of "Ospedali Riuniti Umberto I" in Ancona between December 1, 2021, and March 31, 2022. The patients' medical history and clinical data were collected at T0, before treatment, and at T1, corresponding to the last follow-up visit. Special attention was given to gastrointestinal adverse events (GIRAE). A total of 108 patients were included in the study. At baseline median PASI was 14.8 (range 2.2-27, SD 6.1), and median DLQI was 9.3 (5-16, SD 2.6). The median PASI for treated patients was 0.7 (0-3, SD 0.8; p < 0.00) 1and median DLQI was 0.3 (0-1, SD 0.5; p < 0.001). At T1 54/114 patients (50%) reached PASI100, of the other 54, 48 (88.9%) reached PASI 90 while the other six discontinued for secondary ineffectiveness. Only three patients reported a GIRAE (diarrhea), however, when screened, no IBD was found. Consistent with data in the literature, secukinumab is an effective and safe drug for the treatment of plaque psoriasis also in a real-life experience context. There should be no concern in choosing the drug for fear of possible IBDs-related GIRAE if there is no personal history or familiarity for IBDs.

Role of Daptomycin in Cutaneous Wound Healing: A Narrative Review.

Daptomycin is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and the on-label indications for its use include complicated skin and skin structure infections (cSSSI). We performed a narrative review of the literature with the aim to evaluate the role of daptomycin in the skin wound healing process, proposing our point of view on the possible association with other molecules that could improve the skin healing process. Daptomycin may improve wound healing in MRSA-infected burns, surgical wounds, and diabetic feet, but further studies in humans with histological examination are needed. In the future, the combination of daptomycin with other molecules with synergistic action, such as vitamin E and derivates, IB-367, RNA III-inhibiting peptide (RIP), and palladium nanoflowers, may help to improve wound healing and overcome forms of antibiotic resistance.

The pharmacological treatment and management of hyperhidrosis.

INTRODUCTION: Idiopathic hyperhidrosis is a dysfunctional disorder involving eccrine sweat glands, and its impact on patients' daily quality of life is well known. Unlike some years ago, when only poor effective and safe therapeutic alternatives were available, nowadays, several emerging pharmacological active substances have gained significant space as treatment options. AREAS COVERED: The authors report on, in this narrative review, the emerging data from the literature focusing on the pharmacological treatments to draw up a drug treatment flow chart for patients with idiopathic hyperhidrosis, taking into consideration specific differences among axillary, palmoplantar, and craniofacial hyperhidrosis. EXPERT OPINION: Idiopathic hyperhidrosis, regardless of the site of involvement, remains a functional disorder that places a significant burden on patients. After balancing efficacy against adverse events, systemic therapy, although off-label for all forms of hyperhidrosis, can be an added therapeutic option for patients with insufficient response to topical treatment. Until the pathophysiological mechanisms underlying hyperhidrosis are clear and the etiological therapeutic approach becomes realistic, the greatest challenge in the therapeutic management of hyperhidrotic patients seems to be the search for the most convenient combination between different therapeutic modalities (topical and systemic agents, and botulinum toxins) to achieve long-term control of the disease symptoms.

Real-world outcomes in patients with moderate-to-severe plaque psoriasis treated with guselkumab for up to 1 year.

BACKGROUND: Real-world data on guselkumab, especially at times >6 months, are limited. RESEARCH DESIGN AND METHODS: We performed a longitudinal, retrospective analysis on 307 patients with moderate-severe chronic plaque psoriasis (Psoriasis Area Severity Index [PASI] >10) treated with guselkumab for up to 12 months. MAIN OUTCOME MEASURES: PASI 75, PASI 90, and PASI 100 were assessed at baseline and at 4, 12, 20, 28, 36, 44, and 52 weeks. RESULTS: At 12 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 56.4%, 33.6%, and 24.1% of patients, respectively. At 52 weeks, PASI 75, PASI 90, and PASI 100 were achieved in 82.7%, 68.7%, and 51.1% of patients, respectively. Patients without comorbidities and those naïve to previous biological therapy had better responses. The mean Dermatology Life Quality Index score decreased from 14.0 at baseline to 3.1 at 12 weeks and 1.6 at 6 months, which was maintained at later times. Similar improvements were seen in pruritus visual analog scale. CONCLUSIONS: Guselkumab maintains its efficacy for up to 12 months among responders in a real-world cohort of patients with moderate-severe plaque psoriasis, confirming data from prior real-world studies with smaller cohorts and shorter duration of follow-up.